Does low-dose, transdermal, norethisterone acetate reliably cause endometrial transformation in postmenopausal...

In a prospective study, the symptomatic, psychological and endometrial effects of a combined oestradiol/progestogen transdermal therapeutic system which delivers a low daily dose of norethisterone acetate have been investigated in 18 postmenopausal women. Treatment was given in 28 day cycles. Patients received transdermal oestradiol 50 micrograms/day continuously and transdermal norethisterone acetate, 0.1-0.15 mg/day, was added for 14 days. Treatment was given for between 5 and 7 cycles. One patient discontinued therapy because of a skin reaction. Low dose, transdermal norethisterone acetate caused few adverse symptomatic or psychological side-effects and appeared well tolerated. Fourteen endometrial samples were obtained during the combined (norethisterone acetate/oestradiol) phase of the 5th, 6th or 7th treatment cycle. None showed hyperplastic or malignant change but proliferative endometrium, indicative of an inadequate progestational stimulus, was observed in 4 biopsy samples. Three of these patients had reported breakthrough bleeding during therapy. For these reasons, we regard this dose of transdermal norethisterone acetate as inadequate in combination with transdermal oestradiol 50 micrograms/day for routine use in postmenopausal oestrogen users.